Preparation and applications of artificial mucins in biomedicine

Detwiler, Rachel E.; Kramer, Jessica R.

doi:10.1016/j.cossms.2022.101031

Cited by 8 publications

(10 citation statements)

References 129 publications

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“…Aberrant mucin production is associated with a variety of human pathologies from dry eyes and cystic fibrosis to cancer and infection . Mucins are needed in research models of disease and as therapeutics for lubrication, vaccines, antivirals/antimicrobials, and medical device coatings. − However, development of such models and therapies has been challenged by inherent heterogeneity in mucin structure and limited access to human samples. , An additional challenge is that mucins can be rapidly degraded, which particularly limits therapeutic applications. − Therefore, artificial mucins are an area of emerging research. , Here, we report the synthesis and evaluation of artificial mucins that are structural and chemical analogues of native mucins, bind protein targets via their glycans, and have biodegradation rates that can be finely tuned.…”

Section: Introductionmentioning

confidence: 97%

“…3−7 However, development of such models and therapies has been challenged by inherent heterogeneity in mucin structure and limited access to human samples. 4,8 An additional challenge is that mucins can be rapidly degraded, which particularly limits therapeutic applications. 9−11 Therefore, artificial mucins are an area of emerging research.…”

Section: ■ Introductionmentioning

confidence: 99%

“…9−11 Therefore, artificial mucins are an area of emerging research. 4,8 Here, we report the synthesis and evaluation of artificial mucins that are structural and chemical analogues of native mucins, bind protein targets via their glycans, and have biodegradation rates that can be finely tuned.…”

Section: ■ Introductionmentioning

confidence: 99%

“…43 Current mucin surrogates are typically polysaccharides or synthetic polymers. 4,8 Galactomannans, cellulose derivatives, poly(ethyleneglycol), glycomethacrylates, and glyco-norbornenes have all been utilized attempting to recapitulate the viscoelastic, lubricating, or glycan-presenting properties of mucins. While useful in some applications, these materials have different chemical and physical properties from mucins, leading to macroscopic differences in hydration, network formation, rheological properties, and bioactivity.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Though farm animal mucins are relatively accessible, surrogates are often employed since animal mucins are degradable and poorly defined with batch-to-batch variation affecting experimental reproducibility. , Some mucus models even eliminate mucins altogether and contain only small-molecule nutrients . Current mucin surrogates are typically polysaccharides or synthetic polymers. , Galactomannans, cellulose derivatives, poly(ethyleneglycol), glyco-methacrylates, and glyco-norbornenes have all been utilized attempting to recapitulate the viscoelastic, lubricating, or glycan-presenting properties of mucins. While useful in some applications, these materials have different chemical and physical properties from mucins, leading to macroscopic differences in hydration, network formation, rheological properties, and bioactivity.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Mirror Image Mucins and Thio Mucins with Tunable Biodegradation

2023

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Mucin glycoproteins are the major component of mucus and are integral to the cellular glycocalyx. Mucins play diverse roles in health and disease, are an important element in epithelial tissue models, and have broad therapeutic potential. All mucin applications are currently challenged by their inherent structural heterogeneity and degradation by proteases. In this study, we describe the synthesis and study of chemically defined mucin analogues bearing native glycans. We utilized combinations of enantiomer amino acids and glycan thioether linkages to achieve tunable proteolysis while maintaining cytocompatibility and binding activity. Structural characterization revealed a previously unknown mirror-image helix and sheds light on the molecular drivers of glycoprotein conformation. This work represents an important step toward the development of artificial mucins for biomedical applications.

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Section: Introductionmentioning

confidence: 97%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mirror Image Mucins and Thio Mucins with Tunable Biodegradation

2023

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Mucosa‐Mimetic Materials for the Study of Intestinal Homeostasis and Disease

Donahue

Sahoo

Rudolph

et al. 2023

Adv Healthcare Materials

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Mucus is a viscoelastic hydrogel that lines and protects the epithelial surfaces of the body that houses commensal microbiota and functions in host defense against pathogen invasion. As a first‐line physical and biochemical barrier, intestinal mucus is involved in immune surveillance and spatial organization of the microbiome, while dysfunction of the gut mucus barrier is implicated in several diseases. Mucus can be collected from a variety of mammalian sources for study, however, established methods are challenging in terms of scale and efficiency, as well as with regard to rheological similarity to native human mucus. Therefore, there is a need for mucus‐mimetic hydrogels that more accurately reflect the physical and chemical profile of the in vivo human epithelial environment to enable the investigation of the role of mucus in human disease and interactions with the intestinal microbiome. This review will evaluate the material properties of synthetic mucus mimics to date designed to address the above need, with a focus toward an improved understanding of the biochemical and immunological functions of these biopolymers related to utility for research and therapeutic applications.

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Impact of glycan nature on structure and viscoelastic properties of glycopeptide hydrogels

Proksch,

Dal Colle,

Heinz

et al. 2024

Journal of Peptide Science

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Mucus is a complex biological hydrogel that acts as a barrier for almost everything entering or exiting the body. It is therefore of emerging interest for biomedical and pharmaceutical applications. Besides water, the most abundant components are the large and densely glycosylated mucins, glycoproteins of up to 20 MDa and carbohydrate content of up to 80 wt%. Here, we designed and explored a library of glycosylated peptides to deconstruct the complexity of mucus. Using the well‐characterized hFF03 coiled‐coil system as a hydrogel‐forming peptide scaffold, we systematically probed the contribution of single glycans to the secondary structure as well as the formation and viscoelastic properties of the resulting hydrogels. We show that glycan‐decoration does not affect α‐helix and coiled‐coil formation while it alters gel stiffness. By using oscillatory macrorheology, dynamic light scattering microrheology, and fluorescence lifetime‐based nanorheology, we characterized the glycopeptide materials over several length scales. Molecular simulations revealed that the glycosylated linker may extend into the solvent, but more frequently interacts with the peptide, thereby likely modifying the stability of the self‐assembled fibers. This systematic study highlights the interplay between glycan structure and hydrogel properties and may guide the development of synthetic mucus mimetics.

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Preparation and applications of artificial mucins in biomedicine

Cited by 8 publications

References 129 publications

Mirror Image Mucins and Thio Mucins with Tunable Biodegradation

Mirror Image Mucins and Thio Mucins with Tunable Biodegradation

Mucosa‐Mimetic Materials for the Study of Intestinal Homeostasis and Disease

Impact of glycan nature on structure and viscoelastic properties of glycopeptide hydrogels

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